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Abstract

In a study by Cruse et al. published in BMC Medicine, patients with severe brain damage who were in the Vegetative
or Minimally Conscious States (VS or MCS, respectively) from traumatic and nontraumatic
etiologies had assessments of circadian rhythms using an actigraph, a device worn
on a limb to evaluate circadian rhythmicity, in this population. This is a novel approach
and is being used as a surrogate for polysomnography and other reference standards.
Cruse et al. showed more disruption in circadian rhythms in the VS when compared to the MCS. This
suggests that more brain injury occurs in the areas that control circadian rhythmicity
in VS than in MCS patients. The study provides opportunities for improved prognostication
and rehabilitation strategies in this patient population.

Keywords:

Commentary

The Vegetative and Minimally Conscious States (VS and MCS, respectively) are severe
disorders of consciousness that reflect severe brain dysfunction/damage. Vegetative
patients have preserved vegetative functions (temperature, hemodynamic and hormonal
regulation and breathing) and are awake (with arousability with eye opening and sleep-wake
cycles) but show no behavioral evidence of awareness (no eye contact, tracking, obeying
of commands or emotional responses). Minimally conscious patients show minimal and
limited but definite evidence of some aspect(s) of awareness, for example, visual
tracking, movements or emotional responses triggered by relevant environmental stimuli,
even very simple command-following or verbalization as isolated phenomena.

Cruse and colleagues report the results of actigraphy assessments of circadian sleep-wake
rhythms in patients with VS and MCS in research published in BMC Medicine [1]. They studied patients with traumatic and nontraumatic brain injury at widely ranging
intervals from the ictus (0 to 290 months). Actigraphy uses a watch-shaped device
that is strapped to the arm and is used to measure limb movements in sleep as a surrogate
for estimating the sleep-wake cycle. The actigraphs (or actimeters) can provide patterns
of activity that can be used to outline circadian rhythms [2]. Four distinct aspects of movement are captured: amplitude, acrophase (the point
in the sleep-wake cycle when activity is maximal), the mesor (the mean of the rhythm)
and a goodness-of-fit curve to show the robustness of the circadian rhythm. This methodology
has been previously validated by comparing the results with standard polysomnography
[2].

The principal finding was that as a group VS patients (n = 18) had more significantly
disrupted circadian rhythms than did MCS patients (n = 37).

There may be theoretical advantages and disadvantages in using actigraphy in this
population instead of reference standards of objective measures, such as formal polysomnography
or dim-light melatonin onset, or subjective measures, such as sleep log [3]. There was considerable heterogeneity in the anatomy and severity of the brain damage
among the patients. Polysomnographic sleep staging relies primarily on the electroencephalographic
(EEG) changes over time along with other variables. The EEG records rhythms from the
cerebral cortex. The cortex may be somewhat dissociated from subcortical structures,
namely the hypothalamus and thalamus, which drive the sleep-wake cycle, especially
in cases of severe head injury with diffuse axonal injury. Thus, actigraphy, which
reliably measures the motor output of various sleep and wakefulness stages, may have
an advantage. On the other hand, if the motor pathways are damaged, this may dissociate
motor output from activity of the deep grey structures.

There were confounders present, especially the use of drugs that could alter the EEG,
sleep-wake cycle including sleep staging, but at least these were well documented.

The findings of Cruse et al. [1] are of both theoretical and practical interest. It makes intuitive sense that circadian
rhythms would be more disrupted in patients with VS than MCS as the former state reflects
a greater degree of brain damage than the latter. As the authors mention, the suprachiasmatic
nucleus in the thalamus (the 'pacemaker' for the circadian rhythm) need not be directly
damaged to produce circadian disruption, but is driven to some extent by other structures,
especially the thalamus [4], which is commonly damaged directly or through transsynaptic degeneration [5]. It follows that the degree of circadian rhythm disruption as measured by actigraphy,
in this novel application, may have prognostic significance. The other point, which
seems to be making itself more apparent with advances in technology, is that the clinical
evaluation in severely brain-damaged patients is often inaccurate or misleading [6,7]. Simple eye-opening to differentiate wakefulness from sleep is not always reliable.

There are some exciting prospects for extending this type of research. Combining polysomnography
with actigraphy may address the variable pathologies in brain-injured patients and
allow better characterization and validation of sleep compared to wakefulness. It
would also be of value to study patients serially from the time of ICU admission onwards
to note when true sleep-wake circadian cycles return and to correlate these with other
measures of structure and function to arrive at an earlier prognosis. This may also
help in the selection of patients who could be fast-tracked for early rehabilitation,
which has been shown to improve cognitive and discharge destination outcomes [8].

Abbreviations

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

MS and GBY drafted the editorial and have read and approved the final manuscript.

Authors' information

MS is an Associate Professor in the Department of Medicine, Divisions of Critical
Care Medicine and Respirology/ Sleep Medicine and Schulich School of Medicine and
Dentistry, Western University, London, ON, Canada. She is certified in sleep medicine
and is a Fellow of the American Academy of Sleep Medicine (FAASM) as well as board
certified in Critical Care and Pulmonology in both Canada and the US. She is the Director
of Education for the Royal College of Physicians and Surgeons of Canada (RCPSC) Postgraduate
Residency Training Program for Adult Critical Care, Western University. GBY is a Professor
in Clinical Neurological Sciences specializing in neurocritical care.